In:
Neurodegenerative Diseases, S. Karger AG, Vol. 15, No. 4 ( 2015), p. 243-257
Abstract:
〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 β-Synuclein (β-Syn) is a member of the highly homologous synuclein protein family. The most prominent family member, α-synuclein (α-Syn), abnormally accumulates in so-called Lewy bodies, one of the major pathological hallmarks of α-synucleinopathies. Notably, parts of the peptide backbone, called the nonamyloid component, are also found in amyloid plaques. However, β-Syn seems to have beneficial effects by reducing α-Syn aggregation, and amyloid antiaggregatory activity has been described. 〈 b 〉 〈 i 〉 Objective: 〈 /i 〉 〈 /b 〉 The aim of the study was to analyze if wild-type β-Syn can counteract functional and pathological changes in a murine Alzheimer model over different time periods. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 At the onset of pathology, lentiviral particles expressing human β-Syn were injected into the hippocampus of transgenic mice overexpressing human amyloid precursor protein with Swedish and London mutations (APP 〈 sub 〉 SL 〈 /sub 〉 ). An empty vector served as the control. Behavioral analyses were performed 1, 3 and 6 months after injection followed by biochemical and histological examinations of brain samples. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 β-Syn expression was locally concentrated and rather modest, but nevertheless changed its effect on APP expression and plaque load in a time- and concentration-dependent manner. Interestingly, the phosphorylation of glycogen synthase kinase 3 beta was enhanced in APP 〈 sub 〉 SL 〈 /sub 〉 mice expressing human β-Syn, but an inverse trend was observed in wild-type animals. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 The initially reported beneficial effects of β-Syn could be partially reproduced, but locally elevated levels of β-Syn might also cause neurodegeneration. To enlighten the controversial pathological mechanism of β-Syn, further examinations considering the relationship between concentration and exposure time of β-Syn are needed.
Type of Medium:
Online Resource
ISSN:
1660-2854
,
1660-2862
Language:
English
Publisher:
S. Karger AG
Publication Date:
2015
detail.hit.zdb_id:
2126858-7
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